Patient safety in English general practice : the role of routinely collected data in detecting adverse events

The use of routinely collected, or administrative, data for measuring and monitoring patient safety in primary care is a relatively new phenomenon. With increasing availability of data from different sources and care settings, their application for adverse event surveillance needs evaluation. In this thesis, I demonstrated that data routinely collected from primary care and secondary care can be applied for internal monitoring of adverse events at the general practice-level in England, but these data currently have limited use for safety benchmarking in primary care. To support this statement, multiple approaches were adopted. In the first part of the thesis, the nature and scope of patient safety issues in general practice were defined by evidence from a literature review and informal consultations with general practitioners (GPs). Secondly, using these two methods, measures of adverse events based on routinely collected healthcare data were identified. Thirdly, clinical consensus guided the selection of three candidate patient safety indicators for investigation; the safety issues explored in this thesis were recorded incidents with designated adverse event diagnostic codes and complications associated with two common diseases, emergency admissions for diabetic hyperglycaemic emergencies (diabetic ketoacidosis, DKA and hyperglycaemic hyperosmolar state, HHS) and cancer. In the second part of the thesis, the contributions of routinely collected data to new knowledge about potentially preventable adverse events in England were considered. Data from a primary care trust (NHS Brent), national primary care data (from the General Practice Research Database, GPRD) and secondary care data (Hospital Episode Statistics, HES) were used to explore the epidemiology of, and patient characteristics associated with, coded adverse events and emergency admissions for diabetic hyperglycaemic emergencies and cancer. Low rates of adverse events were found, with variation by individual patient factors. Finally, recommendations were made on extending the uses of routinely collected data for patient safety monitoring in general practice

Detecting transthyretin amyloid cardiomyopathy (ATTR-CM) using machine learning: an evaluation of the performance of an algorithm in a UK setting

Objective: The aim of this study was to evaluate the potential real-world application of a machine learning (ML) algorithm, developed and trained on heart failure (HF) cohorts in the USA, to detect patients with undiagnosed wild type cardiac amyloidosis (ATTRwt) in the UK. // Design: In this retrospective observational study, anonymised, linked primary and secondary care data (Clinical Practice Research Datalink GOLD and Hospital Episode Statistics, respectively, were used to identify patients diagnosed with HF between 2009 and 2018 in the UK. International Classification of Diseases (ICD)-10 clinical modification codes were matched to equivalent Read (primary care) and ICD-10 WHO (secondary care) diagnosis codes used in the UK. In the absence of specific Read or ICD-10 WHO codes for ATTRwt, two proxy case definitions (definitive and possible cases) based on the degree of confidence that the contributing codes defined true ATTRwt cases were created using ML. // Primary outcome measure: Algorithm performance was evaluated primarily using the area under the receiver operating curve (AUROC) by comparing the actual versus algorithm predicted case definitions at varying sensitivities and specificities. // Results: The algorithm demonstrated strongest predictive ability when a combination of primary care and secondary care data were used (AUROC: 0.84 in definitive cohort and 0.86 in possible cohort). For primary care or secondary care data alone, performance ranged from 0.68 to 0.78. // Conclusion: The ML algorithm, despite being developed in a US population, was effective at identifying patients that may have ATTRwt in a UK setting. Its potential use in research and clinical care to aid identification of patients with undiagnosed ATTRwt, possibly enabling earlier diagnosis in the disease pathway, should be investigated

The impact of a national clinician-led audit initiative on care and mortality after hip fracture in England: an external evaluation using time trends in non-audit data.

BACKGROUND: Hip fracture is the most common serious injury of older people. The UK National Hip Fracture Database (NHFD) was launched in 2007 as a national collaborative, clinician-led audit initiative to improve the quality of hip fracture care, but has not yet been externally evaluated. METHODS: We used routinely collected data on 471,590 older people (aged 60 years and older) admitted with a hip fracture to National Health Service (NHS) hospitals in England between 2003 and 2011. The main variables of interest were the use of early surgery (on day of admission, or day after) and mortality at 30 days from admission. We compared time trends in the periods 2003-2007 and 2007-2011 (before and after the launch of the NHFD), using Poisson regression models to adjust for demographic changes. FINDINGS: The number of hospitals participating in the NHFD increased from 11 in 2007 to 175 in 2011. From 2007 to 2011, the rate of early surgery increased from 54.5% to 71.3%, whereas the rate had remained stable over the period 2003-2007. Thirty-day mortality fell from 10.9% to 8.5%, compared with a small reduction from 11.5% to 10.9% previously. The annual relative reduction in adjusted 30-day mortality was 1.8% per year in the period 2003-2007, compared with 7.6% per year over 2007-2011 (P<0.001 for the difference). INTERPRETATION: The launch of a national clinician-led audit initiative was associated with substantial improvements in care and survival of older people with hip fracture in England

Patient information leaflets for placebo-controlled surgical trials : a review of current practice and recommendations for developers

Contributions Sian Cousin: methodology; formal analysis; writing—original draft; writing—review and editing; visualisation. Marc Huttman: data collection, review and editing. Natalie Blencowe: conceptualisation; methodology; formal analysis; writing—original draft; writing—review and editing; visualisation. Carmen Tsang: data collection, review and editing. Daisy Elliott: formal analysis, review and editing. Jane Blazeby: review and editing. David Beard: conceptualisation, review and editing. Marion Campbell: conceptualisation, review and editing. Katie Gillies: conceptualisation; methodology; formal analysis; writing—original draft; writing—review and editing; visualisation.Peer reviewe

Construction of the secondary care administrative records frailty (SCARF) index and validation on older women with operable invasive breast cancer in England and Wales:a cohort study

OBJECTIVES: Studies that use national datasets to evaluate the management of older women with breast cancer are often constrained by a lack of information on patient fitness. This study constructed a frailty index for use with secondary care administrative records and evaluated its ability to improve models of treatment patterns and overall survival in women with breast cancer. DESIGN: Retrospective cohort study. PARTICIPANTS: Women aged ≥50 years with oestrogen receptor (ER) positive early invasive breast cancer diagnosed between 2014 and 2017 in England. METHODS: The secondary care administrative records frailty (SCARF) index was based on the cumulative deficit model of frailty, using International Statistical Classification of Diseases, Injuries and Causes of Death, 10th revision codes to define a set of deficits. The index was applied to administrative records that were linked to national cancer registry datasets. The ability of the SCARF index to improve the performance of regression models to explain observed variation in the rate of surgery and overall survival was evaluated using Harrell's c-statistic and decision curve analysis. External validation was performed on a dataset of similar women diagnosed in Wales. RESULTS: The SCARF index captured 32 deficits that cover functional impairment, geriatric syndromes, problems with nutrition, cognition and mood, and medical comorbidities. In the English dataset (n=67 925), the prevalence of frailty in women aged 50-69, 70-79 and ≥80 years was 15%, 28% and 47%, respectively. Adding a frailty measure to regression models containing age, tumour characteristics and comorbidity improved their ability to: (1) discriminate between whether a woman was likely to have surgery and (2) predict overall survival. Similar results were obtained when the models were applied to the Welsh cohort (n=4 230). CONCLUSION: The SCARF index provides a simple and consistent method to identify frailty in population level data and could help describe differences in breast cancer treatments and outcomes

Reporting of key methodological issues in placebo-controlled trials of surgery needs improvement:a systematic review

OBJECTIVES:To examine key methodological considerations for using a placebo intervention in randomized controlled trials (RCTs) evaluating invasive procedures, including surgery. STUDY DESIGN AND SETTING:RCTs comparing an invasive procedure with a placebo were included in this systematic review. Articles published from database inception to December 31, 2017, were retrieved from Ovid MEDLINE, Ovid EMBASE and CENTRAL electronic databases, by handsearching references and expert knowledge. Data on trial characteristics (clinical area, nature of invasive procedure, number of patients and centers) and key methodological (rationale for using placebos, minimization of risk, information provision, offering the treatment intervention to patients randomized to placebo, delivery of cointerventions, and intervention standardization and fidelity) were extracted and summarized descriptively. RESULTS:One hundred thirteen articles reporting 96 RCTs were identified. Most were conducted in gastrointestinal surgery (n = 40, 42%) and evaluated minimally invasive procedures (n = 44, 46%). Over two-thirds randomized fewer than 100 patients (n = 65, 68%) and a third were single center (n = 31, 32%). A third (n = 33, 34%) did not report a rationale for using a placebo. Most common strategies to minimize patient risk were operator skill (n = 22, 23%) and independent data monitoring (n = 28, 29%). Provision of patient information regarding placebo use was infrequently reported (n = 11, 11%). Treatment interventions were offered to patients randomized to placebo in 43 trials (45%). Cointerventions were inconsistently reported, but 64 trials (67%) stated that anesthesia was matched between groups. Attempts to standardize interventions and monitor their delivery were reported in n = 7, (7%) and n = 4, (4%) trials, respectively. CONCLUSION:Most placebo-controlled trials in surgery evaluate minor surgical procedures and currently there is inconsistent reporting of key trial methods. There is a need for guidance to optimize the transparency of trial reporting in this area

Inhibition of NOX1 mitigates blood pressure increases in elastin insufficiency

Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams-Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams-Beuren syndrome deletions, which extended to include th

Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer

© 2018, Hong Kong Academy of Medicine Press. All rights reserved. Introduction: The management of human epidermal growth factor receptor 2 (HER2)–positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. Methods: This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. Results: Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3-9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. Conclusions: In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.Link_to_subscribed_fulltex

A framework for variable content document generation with multiple actors

“NOTICE: this is the author’s version of a work that was accepted for publication in Information and Software Technology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Information and Software Technology, Volume 56, Issue 9, September 2014, Pages 1101–1121 DOI10.1016/j.infsof.2013.12.006Context - Advances in customization have highlighted the need for tools supporting variable content document management and generation in many domains. Current tools allow the generation of highly customized documents that are variable in both content and layout. However, most frameworks are technology-oriented, and their use requires advanced skills in implementation-related tools, which means their use by end users (i.e. document designers) is severely limited. Objective - Starting from past and current trends for customized document authoring, our goal is to provide a document generation alternative in which variants are specified at a high level of abstraction and content reuse can be maximized in high variability scenarios. Method Based on our experience in Document Engineering, we identified areas in the variable content document management and generation field open to further improvement. We first classified the primary sources of variability in document composition processes and then developed a methodology, which we called DPL based on Software Product Lines principles to support document generation in high variability scenarios. Results - In order to validate the applicability of our methodology we implemented a tool DPLfw to carry out DPL processes. After using this in different scenarios, we compared our proposal with other state-of-the-art tools for variable content document management and generation. Conclusion - The DPLfw showed a good capacity for the automatic generation of variable content documents equal to or in some cases surpassing other currently available approaches. To the best of our knowledge, DPLfw is the only framework that combines variable content and document workflow facilities, easing the generation of variable content documents in which multiple actors play different roles.This work has been partially funded by the Spanish Ministerio de Economia y Competitividad under Grant TIPEx (TIN2010-19859-C03-03).Gómez Llana, A.; Penadés Gramage, MC.; Canos Cerda, JH.; Borges, MR.; Llavador Campos, M. (2014). A framework for variable content document generation with multiple actors. Information and Software Technology. 56(9):1101-1121. https://doi.org/10.1016/j.infsof.2013.12.006S1101112156

Surgery and adjuvant radiotherapy for unilateral ductal carcinoma in situ (DCIS) in women aged over 70 years: A population based cohort study.

BACKGROUND: There is little clinical evidence to guide treatment decisions for ductal carcinoma in situ (DCIS) in older women. This study evaluated how the management of DCIS in women aged 70 or more compared with women aged 50-69 in England and Wales. METHOD: The study identified women aged ≥50 years with new unilateral DCIS diagnosed between 2014 and 2016 from linked cancer registration and routine hospital datasets for England and Wales. Rates of surgery and adjuvant radiotherapy were examined by age, deprivation, fitness measures (comorbidity and frailty), method of presentation and tumour grade using multilevel logistic regression. RESULTS: 12,716 women were diagnosed with unilateral DCIS between 2014 and 2016, of whom 2,754 (22%) were aged ≥70 years and 74% were screen detected. High grade DCIS was common, irrespective of age and method of presentation. Fewer women aged ≥70 had surgery compared to women aged 50-69 (81% vs. 94%), which was only partly explained by poor fitness. Use of radiotherapy following breast conserving surgery was strongly associated with grade, and was received by less than 16% of all patients with low grade tumours. Over 70% of women aged 50-69 with high grade DCIS received radiotherapy, but this fell to 35% among women aged ≥80. Use of radiotherapy was not associated with patient fitness. CONCLUSION: Treatment decisions for women with DCIS varied by age at diagnosis. Lower rates of surgery and adjuvant radiotherapy in older women were only partly explained by patient fitness. Better evidence is needed to aid treatment selection for older women with DCIS